Giant cell-rich osteosarcoma(GCRO)is a special subtype of osteosarcoma,and is rare.This paper reported the clinical and imaging data of the patient with GCRO who had special imaging manifestations,and to provide the reference for clinical diagnosis and treatment of GCRO.The patient,a 69-year-old female,was admitted to the hospital due to the discovery of a mass in the right lower leg for 1 month.The X-ray imaging manifestations showed that the cortical bones on the opposite edges of the tibia and fibula presented mild moth-eaten changes.The plain CT scan imaging manifestations showed that there was a mass within the muscle,and the cortical bones on the opposite edges of the tibia and fibula were destroyed.The tumor only involved the superficial cortical bones and did not invade the deep cortical bones and the medullary cavity.The MRI imaging manifestations showed that the local bones of the tibia and fibula adjacent to the tumor were destroyed,and the medullary cavity was not invaded.An extended resection of the mass was performed,and the postoperative pathological diagnosis was GCRO.The patient received chemotherapy after the operation.However,a tumor in the right lower leg recurred 15 months after the operation.The patient passed away 21 months after the operation.Giant cell-rich osteosarcoma often leads to misdiagnosis or missed diagnosis due to its non-specific clinical manifestations.This paper explored the clinical manifestations and imaging data of the patient with GCRO in order to improve the clinical understanding level and the level of diagnosis and treatment of the clinicians about this disease.

Working memory is an executive memory process that includes encoding, maintenance, and retrieval. These processes can be modulated by transcranial alternating current stimulation (tACS) with sinusoidal waves. However, little is known about the impact of the rate of current change on working memory. In this study, we aimed to investigate the effects of two types of tACS with different rates of current change on working memory performance and brain activity. We applied a randomized, single-blind design and divided 81 young participants who received triangular wave tACS, sinusoidal wave tACS, or sham stimulation into three groups. Participants performed n-back tasks, and electroencephalograms were recorded before, during, and after active or sham stimulation. Compared to the baseline, working memory performance (accuracy and response time) improved after stimulation under all stimulation conditions. According to drift-diffusion model analysis, triangular wave tACS significantly increased the efficiency of non-target information processing. In addition, compared with sham conditions, triangular wave tACS reduced alpha power oscillations in the occipital lobe throughout the encoding period, while sinusoidal wave tACS increased theta power in the central frontal region only during the later encoding period. The brain network connectivity results showed that triangular wave tACS improved the clustering coefficient, local efficiency, and node degree intensity in the early encoding stage, and these parameters were positively correlated with the non-target drift rate and decision starting point. Our findings on how tACS modulates working memory indicate that triangular wave tACS significantly enhances brain network connectivity during the early encoding stage, demonstrating an improvement in the efficiency of working memory processing. In contrast, sinusoidal wave tACS increased the theta power during the later encoding stage, suggesting its potential critical role in late-stage information processing. These findings provide valuable insights into the potential mechanisms by which tACS modulates working memory.
Humans ; Memory, Short-Term/physiology* ; Male ; Female ; Young Adult ; Transcranial Direct Current Stimulation/methods* ; Brain/physiology* ; Adult ; Electroencephalography ; Single-Blind Method

Objective:To study the relationship between the polarization state of hippocampal microglia and depression-like behavior in mice and the regulatory effect of Xiaoyaosan.Methods:Sixty female BALB/C mice were randomly divided into control group, model group, Xiaoyaosan group and fluoxetine group according to the random number method with 15 in each group. Except for control group, the mice in the other 3 groups received chronic restraint stress for 21 days to establish the depressive model. The mice in the Xiaoyaosan group and fluoxetine group were gavaged with Xiaoyaosan(28.06 g/kg) and fluoxetine(3.03 mg/kg) respectively, while the mice in control and model groups received the same volume of 0.9% NaCl solution. Mouse behaviors were evaluated by sucrose preference test and elevated plus maze test.ELISA was used to detect the contents of 5-hydroxytryptamine(5-HT), dopamine(DA) in serum and transforming growth factor-β1(TGF-β1), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the hippocampus. Immunohistochemistry was used to detect inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) expression.Western blot was used to detect the protein levels of iNOS, Arg-1, CD86 and CD206. The mRNA expression of iNOS and Arg-1 in hippocampus was detected by qRT-PCR. The pathological changes of hippocampus were observed by HE staining.SPSS 27.0 software was used to analyze the data. One-way ANOVA was used for comparison among multiple groups, and LSD test was used for pairwise comparison.Results:(1) There were significant differences in sucrose preference among the 4 groups ( F=46.62, P<0.05).The sucrose preference of model group was lower than that of the control group ( P<0.05), while the sucrose preference of Xiaoyaosan group was higher than that of the model group ( P<0.05).There were significant differences in the number of open arm entries and residence time in the elevated plus maze test among the 4 groups ( F=24.63, 26.94, both P<0.05). The number of open arm entries and residence time in model group ((1.80±1.48)times, (6.19±1.67)s) were lower than those of the control group ((9.80±1.64)times, (56.81±2.75)s)) (both P<0.05). The number of open arm entries and residence time in Xiaoyaosan group ((6.80±0.84)times, (29.59±7.72)s) were significantly higher than model group(both P<0.05).(2) There were significant differences in serum 5-HT and DA levels among the 4 groups ( F=33.27, 76.03, both P<0.05). The serum 5-HT and DA levels in the model group were lower than those of the control group (both P<0.05).The serum 5-HT and DA levels in the Xiaoyaosan group were higher than those of model group (both P<0.05).(3)There were significant differences in the contents of TGF-β1, IL-10, TNF-α and IL-6 in the hippocampus of 4 groups ( F=31.93, 64.01, 25.74, 28.14, all P<0.05). The contents of TGF-β1 and IL-10 in the model group were lower than those of the control group, while the contents of TNF-α and IL-6 were higher (all P<0.05). Compared with the model group, the contents of TGF-β1 and IL-10 in Xiaoyaosan group ( TGF-β1: (30.40±1.56)pg/mL vs (23.77±2.24) pg/mL; IL-10: ((233.94±11.38)pg/mL) vs (130.46±15.34) pg/mL) were higher, and the contents of TNF-α ((73.35±1.51)ng/mL vs (85.89±4.52)pg/mL) and IL-6 (66.15±2.96)pg/mL vs (76.01±1.59)pg/mL) )were lower (all P<0.05).(4)The results of qRT-PCR, immunohistochemistry and Western blot all showed that there were significant differences in mRNA and protein levels of iNOS ( F=41.92, 20.78, 9.27, all P<0.05) and Arg-1 ( F=27.24, 24.23, 6.49, all P<0.05) in the hippocampus among the 4 groups of mice. The mRNA and protein levels of iNOS of the model group were higher than those in the control group (both P<0.05), while the mRNA and protein levels of Arg-1 were lower than those in the control group(both P<0.05).The mRNA and protein levels of iNOS in the Xiaoyaosan group were lower than those in the model group (both P<0.05), while the mRNA and protein levels of Arg-1 were higher than model group(both P<0.05).(5) The expressions of CD206 and CD86 in hippocampus of the 4 groups were significantly different ( F=86.14, 24.02, both P<0.05). Compared with the control group, the model group had a higher expression of CD86 in the hippocampus and a lower expression of CD206 (both P<0.05).Compared with the model group, the CD86 of Xiaoyaosan group was lower, while CD206 was higher (both P<0.05). (6) The HE staining results showed that the cells in the hippocampal CA1 region of the model group mice exhibited disordered arrangement, fewer cells, larger intercellular space, unclear boundary and other changes.The morphology of the cells in the Xiaoyaosan group was improved compared to the model group. Conclusion:Xiaoyaosan can inhibit M1 activation of microglia and neuronal damage in the hippocampus of mice caused by chronic restraint stress, exerting neuroprotective effects and improving depressive behavior in mice.

Objective:To study the relationship between the polarization state of hippocampal microglia and depression-like behavior in mice and the regulatory effect of Xiaoyaosan.Methods:Sixty female BALB/C mice were randomly divided into control group, model group, Xiaoyaosan group and fluoxetine group according to the random number method with 15 in each group. Except for control group, the mice in the other 3 groups received chronic restraint stress for 21 days to establish the depressive model. The mice in the Xiaoyaosan group and fluoxetine group were gavaged with Xiaoyaosan(28.06 g/kg) and fluoxetine(3.03 mg/kg) respectively, while the mice in control and model groups received the same volume of 0.9% NaCl solution. Mouse behaviors were evaluated by sucrose preference test and elevated plus maze test.ELISA was used to detect the contents of 5-hydroxytryptamine(5-HT), dopamine(DA) in serum and transforming growth factor-β1(TGF-β1), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the hippocampus. Immunohistochemistry was used to detect inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) expression.Western blot was used to detect the protein levels of iNOS, Arg-1, CD86 and CD206. The mRNA expression of iNOS and Arg-1 in hippocampus was detected by qRT-PCR. The pathological changes of hippocampus were observed by HE staining.SPSS 27.0 software was used to analyze the data. One-way ANOVA was used for comparison among multiple groups, and LSD test was used for pairwise comparison.Results:(1) There were significant differences in sucrose preference among the 4 groups ( F=46.62, P<0.05).The sucrose preference of model group was lower than that of the control group ( P<0.05), while the sucrose preference of Xiaoyaosan group was higher than that of the model group ( P<0.05).There were significant differences in the number of open arm entries and residence time in the elevated plus maze test among the 4 groups ( F=24.63, 26.94, both P<0.05). The number of open arm entries and residence time in model group ((1.80±1.48)times, (6.19±1.67)s) were lower than those of the control group ((9.80±1.64)times, (56.81±2.75)s)) (both P<0.05). The number of open arm entries and residence time in Xiaoyaosan group ((6.80±0.84)times, (29.59±7.72)s) were significantly higher than model group(both P<0.05).(2) There were significant differences in serum 5-HT and DA levels among the 4 groups ( F=33.27, 76.03, both P<0.05). The serum 5-HT and DA levels in the model group were lower than those of the control group (both P<0.05).The serum 5-HT and DA levels in the Xiaoyaosan group were higher than those of model group (both P<0.05).(3)There were significant differences in the contents of TGF-β1, IL-10, TNF-α and IL-6 in the hippocampus of 4 groups ( F=31.93, 64.01, 25.74, 28.14, all P<0.05). The contents of TGF-β1 and IL-10 in the model group were lower than those of the control group, while the contents of TNF-α and IL-6 were higher (all P<0.05). Compared with the model group, the contents of TGF-β1 and IL-10 in Xiaoyaosan group ( TGF-β1: (30.40±1.56)pg/mL vs (23.77±2.24) pg/mL; IL-10: ((233.94±11.38)pg/mL) vs (130.46±15.34) pg/mL) were higher, and the contents of TNF-α ((73.35±1.51)ng/mL vs (85.89±4.52)pg/mL) and IL-6 (66.15±2.96)pg/mL vs (76.01±1.59)pg/mL) )were lower (all P<0.05).(4)The results of qRT-PCR, immunohistochemistry and Western blot all showed that there were significant differences in mRNA and protein levels of iNOS ( F=41.92, 20.78, 9.27, all P<0.05) and Arg-1 ( F=27.24, 24.23, 6.49, all P<0.05) in the hippocampus among the 4 groups of mice. The mRNA and protein levels of iNOS of the model group were higher than those in the control group (both P<0.05), while the mRNA and protein levels of Arg-1 were lower than those in the control group(both P<0.05).The mRNA and protein levels of iNOS in the Xiaoyaosan group were lower than those in the model group (both P<0.05), while the mRNA and protein levels of Arg-1 were higher than model group(both P<0.05).(5) The expressions of CD206 and CD86 in hippocampus of the 4 groups were significantly different ( F=86.14, 24.02, both P<0.05). Compared with the control group, the model group had a higher expression of CD86 in the hippocampus and a lower expression of CD206 (both P<0.05).Compared with the model group, the CD86 of Xiaoyaosan group was lower, while CD206 was higher (both P<0.05). (6) The HE staining results showed that the cells in the hippocampal CA1 region of the model group mice exhibited disordered arrangement, fewer cells, larger intercellular space, unclear boundary and other changes.The morphology of the cells in the Xiaoyaosan group was improved compared to the model group. Conclusion:Xiaoyaosan can inhibit M1 activation of microglia and neuronal damage in the hippocampus of mice caused by chronic restraint stress, exerting neuroprotective effects and improving depressive behavior in mice.

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective To investigate the progression of breast cancer in mice induced by chronic binding stress and the regulatory mechanism of Xiaoyao SAN based on TGF-β1/CD147 signal pathway.Methods 40 BABL/c mice were randomly divided into tumor group,model group,Xiaoyaosan group and Mifepristone group,and then 4T1 cell line was inoculated into the armpits of each group of mice.After Tumor formation,mice in all groups except tumor group were subjected to chronic restraint stress for 21 days.Meanwhile,mice in Xiaoyaosan and Mifepristone groups were gavaged with the corresponding drugs,and mice in the other two groups were gavaged with normal saline.After the modeling,the mice were sacrificed after anaesthesia.The weight and volume of the tumors and visceral index of the mice were measured.The contents of serum tumor markers(CA199,CEA,VEGF),serum neurotransmitters(DA and CORT),and inflammatory mediators(TGF-β1 and IL-10)in tumor tissues were detected by Elisa.The expressions of iNOS and Arg-1,the polarization markers of macrophages,and the expressions of CD147 and its downstream signaling molecules MMP2,MMP9 and VEGF in tumor tissues were all detected by immunohistochemistry and Western blot.Results Compared with tumor group,in model group,tumor weight and volume,serum CA199,CEA,VEGF,CORT content,tumor TGF-β1 and IL-10 content were significantly increased;visceral index and serum DA content were significantly reduced;the expression of M2-type polarization marker Arg-1 in tumor macrophages was significantly increased,while the expression of M1-type polarization marker iNOS was significantly decreased;the expressions of CD147 and its downstream signaling molecules MMP2,MMP9 and VEGF were significantly increased.Both Xiaoyaosan and mifepristone could effectively reverse the above changes.Conclusion The mechanism of chronic restraint stress promoting breast cancer progression in mice is related to the increased release of TGF-β1 from M2-type polarization of tumor-associated macrophages,which activates CD147 and its downstream related signals.Xiaoyaosan could relieve the M2-type polarization of macrophages caused by increased corticosterone under stress conditions,reduce the production of TGF-β1,inhibit CD147 and its downstream signal,and thus inhibit the progression of breast cancer caused by chronic restraint stress in mice.

The retrosplenial cortex has been implicated in processing sensory information and spatial learning, with abnormal neural activity reported in association with psychedelics and in mouse and non-human primate models of autism spectrum disorders (ASDs). The direct role of the retrosplenial cortex in regulating social behaviors remains unclear. In this work, we reveal that neural activity in the retrosplenial agranular cortex (RSA), a subregion of the retrosplenial cortex, is initially activated, then quickly suppressed upon social contact. This up-down phase of RSA neurons is crucial for normal social behaviors. Parvalbumin-positive GABAergic neurons in the hippocampal CA1 region were found to send inhibitory projections to the RSA. Blocking these CA1-RSA inhibitory inputs significantly impaired social behavior. Notably, enhancing the CA1-RSA inhibitory input rescued the social behavior defects in an ASD mouse model. This work suggests a neural mechanism for the salience processing of social behavior and identifies a potential target for ASD intervention using neural modulation approaches.
Animals ; Social Behavior ; CA1 Region, Hippocampal/physiology* ; Mice ; Male ; Autism Spectrum Disorder/physiopathology* ; Mice, Inbred C57BL ; GABAergic Neurons/drug effects* ; Neural Inhibition/drug effects* ; Parvalbumins/metabolism* ; Neural Pathways/physiology* ; Cerebral Cortex/physiology*

Pathological mood changes,mainly depression,occurring during the diagnosis and treatment of breast cancer are referred to as breast cancer-related depression(BCRD).Numerous epidemiological and clinical studies have confirmed that BCRD is a complex condition that is difficult to treat and has a poor prognosis.Most existing clinical treatments involve the use of postoperative chemotherapy for breast cancer,and antidepressant drugs,which treat breast cancer and depression as two independent diseases and have various disadvantages such as low efficiency and strong adverse reactions.Traditional Chinese Medicine(TCM)has a unique value in the prevention and treatment of BCRD via its ability to regulate multiple pathways and targets using multiple components at the same time.In this paper,we review the mechanism of BRCD and the therapeutic mechanisms of TCM from the aspects of neurological disorders,inflammatory immune response,and intestinal flora disorders,with a view to providing references for the clinical application and research of TCM in the treatment of BCRD.

Objective To observe the influence of Creb protein over-expression and under-expression in the prefrontal cortex on depressive behavior in rats.Methods Adeno-associated virus(AAV)strains that can knock down Creb expression in the prefrontal cortex of rats were injected using the stereotaxic injection method and screened by Western blot,reverse transcription quantitative polymerase chain reaction(RT-qPCR)and immunofluorescence.Forty rats were divided randomly into Control,chronic restraint stress(CRS),CRS combined with AAV interference(CRS+AAVI),and CRS combined with AAV overexpression(CRS+AAVO)groups.The body weight and food intake of the rats in each group were monitored during establishment of the animal model.After establishment of the model,behavioral changes in the rats were monitored by sucrose preference,elevated plus maze,forced swimming,and open field tests.The 5-hydroxytryptamine(5-HT),norepinephrine(NE),and corticosterone(CORT)contents in the prefrontal cortex of rats in each group were measured by enzyme-linked immunosorbent assay.Results Western blot and immunofluorescence showed that Creb protein expression was significantly reduced in the short hairpin RNA2(shRNA2)knockdown groups compared with the other groups(P＜0.05).RT-qPCR showed that Creb mRNA expression was also significantly reduced compared with the other three groups(P＜0.01).The AAV-CREB1-shRNA2 virus strain was therefore selected for subsequent Creb-knockdown experiments in this study.After modeling,the food intake of rats in the CRS+AAVI group was significantly reduced compared with the other groups(P＜0.01).Rats in this group also showed slow weight gain and decreased desire to explore new environments,significantly increased despair and nervous behavior,and significantly decreased 5-HT and NE levels(P＜0.01)and significantly increased CORT levels in the prefrontal cortex(P＜0.01).These depressive behaviors and associated neurotransmitter levels were reversed in the CRS+AAVO group.Conclusions Lower expression of Creb in the prefrontal cortex can aggravate the degree of depression in rats,while high expression of Creb can alleviate depression to a certain extent.These result confirm that Creb expression in the prefrontal cortex is an important target in the pathogenesis of depression,thus providing ideas and references for the construction of animal gene models and further studies of the pathogenesis of depression.